The objective of this proposal is to isolate antibody molecules capable of proteolytic cleavage of their cognate antigen. An E. coli selection system has been devised to identify these antibodies. Large antibody libraries can be made and screened in E. coli using the ImmunoZapTM technology, and this directed approach to the isolation of rare antibodies with proteolytic activity may lead to new types of therapeutic agents for combating certain infections and diseases.